Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-&#947; (IFN&#947;). IFN&#947; has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-&#946; (A&#946;) on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFN&#947;, IL-2, monocyte chemoattractant protein-1 (MCP-1) and IFN&#947;-induced protein 10 kDa (IP-10)), expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK) cells are a major source of IFN&#947; in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and A&#946;-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2) by releasing IFN&#947;. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and A&#946;-treated rats. This was paralleled by a decrease in IFN&#947;, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and A&#946;-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

Item Type:

Journal Article

Full metadata record

DC Field

Value

Language

dc.contributor.author

Lyons, Anthony

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dc.contributor.author

Murphy, Kevin J

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dc.contributor.author

Clarke, Rachael

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dc.contributor.author

Lynch, Marina A

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dc.date.accessioned

2011-04-15T09:22:53Z

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dc.date.available

2011-04-15T09:22:53Z

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dc.date.issued

2011-03-31

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dc.identifier

http://dx.doi.org/10.1186/1742-2094-8-27

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dc.identifier.citation

Journal of Neuroinflammation. 2011 Mar 31;8(1):27

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dc.identifier.uri

http://hdl.handle.net/10147/128131

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dc.description.abstract

Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-&#947; (IFN&#947;). IFN&#947; has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-&#946; (A&#946;) on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFN&#947;, IL-2, monocyte chemoattractant protein-1 (MCP-1) and IFN&#947;-induced protein 10 kDa (IP-10)), expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK) cells are a major source of IFN&#947; in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and A&#946;-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2) by releasing IFN&#947;. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and A&#946;-treated rats. This was paralleled by a decrease in IFN&#947;, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and A&#946;-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.